Mx proteins, dynamin, VPS1/SPO15, and MGM1 are members of a newly described family of large GTPases (Mr=70,000 to 100,000) which are approximately 50% identical in their amino-terminal halves but which have diverse biological activities. The alpha/beta interferon induced Mx proteins confer resistance to specific RNA viruses, most notably influenza viruses. The constitutively expressed dynamin proteins are involved in the constriction of endocytotic vesicles. The yeast VPS1/SP015 protein is essential for exocytosis and spindle pole body separation during meiosis. The yeast MGM1 protein is required for maintenance of mitochondrial DNA. Of specific interest to us are the biological and cellular functions of the vertebrate members of this family: Mx proteins and dynamin. With regard to Mx proteins, topics of interest include identification of the intracellular pathway Mx proteins play a role in, biochemical characterization of their GTPase activity, and determination of parameters that affect their antiviral activity and specificity. Current work is aimed at identifying and characterizing cellular proteins that interact with Mx proteins. With regard to dynamin, our work focuses on the generation of a genetic model for the biological role of the neuron specific dynamin-1 in mice through homologous recombination in embryonic stem (ES) cells. We have already generated animals that carry a mutated dynamin-1 allele, and are currently breeding these animals to homozygosity. If a phenotype is observed in homozygous mice, it may help us to understand how irregularities in the endocytic pathway can precipitate neurologic dysfunction.